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1.
Sports Biomech ; : 1-21, 2024 Sep 16.
Artículo en Inglés | MEDLINE | ID: mdl-39279737

RESUMEN

INTRODUCTION: Stiffness (k) describes a material's resistance to deformation and is useful for understanding neuromuscular function, performance, and injury risk. The aim of this study is to compare the lower limb stiffness method (kLLS), which uses only force plate data, with methods combining force plate and motion capture data to calculate stiffness during the eccentric phase of a countermovement. MATERIAL AND METHODS: Twelve resistance-trained males: age 24.9 (4.4) years, height 1.81 (0.05) m, weight 88.2 (14) kg) performed three maximal effort countermovement jumps (CMJ). Data were collected synchronously using three-dimensional (3D) kinematic and kinetic data (dual force plate setup). Lower limb stiffness (z), joint stiffness (x, y, and z), and leg stiffness (linear, sagittal plane, and 3D) were calculated for the eccentric phase of all CMs. RESULTS: kLLS showed high concurrent validity with strong correlations to kinetic-kinematic methods (r = 0.90-0.97, p < 0.05). A linear mixed model revealed no significant differences in k-values between kLLS and leg stiffness, indicating high concurrent validity. DISCUSSION: kLLS offers valid and valuable information affecting performance, injury risk, and return-to-sport decisions. CONCLUSION: The findings suggest that kLLS is a valid method for calculating stiffness in CMJs and equal to 3D leg stiffness.

2.
J Rehabil Assist Technol Eng ; 9: 20556683221131557, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-36225652

RESUMEN

The aim of this study was to estimate and compare the muscular metabolic power produced in the human body using musculoskeletal inverse-dynamics during cross-country sit-skiing. Two sitting positions were adapted for athletes with reduced trunk and hip muscle control, knee low with frontal trunk support (KL-fix), and knee high (KH). Five female national class able-bodied cross-country skiers performed submaximal and maximal exercise in both sitting positions, while recording 3-D kinematics, pole forces, electromyography and respiratory variables. Simulations were performed from these experimental results and muscular metabolic power was computed. The main part of the muscle metabolic power was produced in the upper limbs for both sitting positions, but KH produced more muscle metabolic power in lower limbs and trunk during maximal intensity. KH was also more efficient, utilizing less muscular metabolic power during submaximal intensities, relatively less power in the upper limbs and more power in the trunk, hip and lower limb muscles. This implies that sitting position KH is preferable for high power output when using able-bodied simulation models. This study showed the potential of using musculoskeletal simulations to improve the understanding of how different equipment design and muscles contribute to performance.

3.
Strahlenther Onkol ; 198(7): 630-638, 2022 07.
Artículo en Inglés | MEDLINE | ID: mdl-35389076

RESUMEN

PURPOSE: Adjuvant radiotherapy (RT) for breast cancer is associated with an increased risk of ischemic heart disease. We examined the risk of coronary artery stenosis in a large cohort of women with breast cancer receiving adjuvant RT. METHODS: A cohort of women diagnosed with breast cancer between 1992 and 2012 in three Swedish health care regions (n = 57,066) were linked to the Swedish Coronary Angiography and Angioplasty Registry (SCAAR) to identify women receiving RT who subsequently underwent a percutaneous coronary intervention (PCI) due to coronary stenosis. Cox regression analyses were performed to examine risk of a coronary intervention and competing risk analyses were performed to calculate cumulative incidence. RESULTS: A total of 649 women with left-sided breast cancer and 494 women with right-sided breast cancer underwent a PCI. Women who received left-sided RT had a significantly higher risk of a PCI in the left anterior descending artery (LAD) compared to women who received right-sided RT, hazard ratio (HR) 1.44 (95% confidence interval [CI] 1.21-1.77, p < 0.001). For the proximal, mid, and distal LAD, the HRs were 1.60 (95% CI 1.22-2.10), 1.38 (95% CI 1.07-1.78), and 2.43 (95% CI 1.33-4.41), respectively. The cumulative incidence of coronary events at 25 years from breast cancer diagnosis were 7.0% in women receiving left-sided RT and 4.4% in women receiving right-sided RT. CONCLUSION: Implementing and further developing techniques that lower cardiac doses is important in order to reduce the risk of long-term side effects of adjuvant RT for breast cancer.


Asunto(s)
Neoplasias de la Mama , Estenosis Coronaria , Intervención Coronaria Percutánea , Neoplasias de Mama Unilaterales , Neoplasias de la Mama/complicaciones , Neoplasias de la Mama/epidemiología , Neoplasias de la Mama/radioterapia , Estenosis Coronaria/epidemiología , Estenosis Coronaria/etiología , Vasos Coronarios , Femenino , Humanos , Intervención Coronaria Percutánea/efectos adversos , Radioterapia Adyuvante/efectos adversos , Neoplasias de Mama Unilaterales/complicaciones , Neoplasias de Mama Unilaterales/epidemiología , Neoplasias de Mama Unilaterales/radioterapia
4.
EClinicalMedicine ; 47: 101398, 2022 May.
Artículo en Inglés | MEDLINE | ID: mdl-35480071

RESUMEN

Background: We have addressed health equity attained by fecal immunochemical testing (FIT) and primary colonoscopy (PCOL), respectively, in the randomised controlled screening trial SCREESCO conducted in Sweden. Methods: We analysed data on the individuals recruited between March 2014, and March 2020, within the study registered with ClinicalTrials.gov, NCT02078804. Swedish population registry data on educational level, household income, country of birth, and marital status were linked to each 60-year-old man and woman who had been randomised to two rounds of FIT 2 years apart (n = 60,123) or once-only PCOL (n = 30,390). Furthermore, we geo-coded each study individual to his/her residential area and assessed neighbourhood-level data on deprivation, proportion of non-Western immigrants, population density, and average distance to healthcare center for colonoscopy. We estimated adjusted associations of each covariate with the colonoscopy attendance proportion out of all invited to respective arms; ie, the preferred outcome for addressing health equity. In the FIT arm, the test uptake and the colonoscopy uptake among the test positives were considered as the secondary outcomes. Findings: We found a marked socioeconomic gradient in the colonoscopy attendance proportion in the PCOL arm (adjusted odds ratio [95% credibility interval] between the groups categorised in the highest vs. lowest national quartile for household income: 2·20 [2·01-2·42]) in parallel with the gradient in the test uptake of the FIT × 2 screening (2·08 [1·96-2·20]). The corresponding gradient in the colonoscopy attendance proportion out of all invited to FIT was less pronounced (1·29 [1·16-1·42]), due to higher proportions of FIT positives in socioeconomically disadvantaged groups. Interpretation: The unintended risk of exacerbating inequalities in health by organised colorectal cancer screening may be higher with a PCOL strategy than a FIT strategy, despite parallel socioeconomic gradients in uptake. Funding: This work was supported by the Swedish Cancer Society under Grant 20 0719. CB and US provided economic support from the Swedish Research Council for Health, Working life, and Welfare under Grant 2020-00962.

6.
Breast Cancer Res Treat ; 172(1): 167-177, 2018 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-30030708

RESUMEN

PURPOSE: To examine factors associated with non-adherence during 5 years of endocrine treatment, including the possible influence of comorbidity burden and specific medical conditions. METHODS: From all women diagnosed with stage I-III, ER-positive breast cancer in Stockholm-Gotland, Uppsala-Örebro and Northern Sweden between 2006 and 2009, we included 4645 women who had at least one dispensation of tamoxifen or aromatase inhibitors (AIs) and 5 years of follow-up without distant recurrence. A medical possession ratio of < 80% was used to define non-adherence. Logistic regression was used to estimate odds ratios (ORs) and 95% confidence intervals (CIs) of non-adherence. RESULTS: During follow-up, 977 (21%) women became non-adherents. Non-adherence was associated with greater comorbidity burden assessed by Charlson comorbidity index (CCI) during follow-up (OR 1.43; 95% CI 1.08-1.88 for ≥ 2 additional scores compared to 0), pre-diagnostic HRT use (OR 1.99; 1.58-2.49), not married (OR 1.42; 1.23-1.64), high educational level (OR 1.25; 1.02-1.53 compared to lowest level), and use of symptom-relieving drugs. HER-2 positivity (OR 0.61; 0.45-0.81) and adjuvant chemotherapy (OR 0.42; 0.35-0.52) were associated with lower odds of non-adherence. Similar patterns were observed for the presence of lymph node metastasis, higher tumour grade, and use of AIs compared to tamoxifen. Myocardial infarction and chronic pulmonary disease was suggested as leading conditions associated with non-adherence in women with increasing CCI. CONCLUSION: We identified subgroups of women with breast cancer at increased risk of non-adherence. Our findings related to comorbidity suggest the importance of focusing on the presence of specific co-existing conditions when monitoring adherence.


Asunto(s)
Antineoplásicos Hormonales/administración & dosificación , Inhibidores de la Aromatasa/administración & dosificación , Neoplasias de la Mama/tratamiento farmacológico , Recurrencia Local de Neoplasia/tratamiento farmacológico , Adulto , Anciano , Antineoplásicos Hormonales/efectos adversos , Inhibidores de la Aromatasa/efectos adversos , Neoplasias de la Mama/epidemiología , Neoplasias de la Mama/patología , Quimioterapia Adyuvante/efectos adversos , Comorbilidad , Femenino , Humanos , Metástasis Linfática , Cumplimiento de la Medicación , Persona de Mediana Edad , Recurrencia Local de Neoplasia/epidemiología , Recurrencia Local de Neoplasia/patología , Suecia/epidemiología , Tamoxifeno/efectos adversos , Tamoxifeno/uso terapéutico
7.
J Appl Biomech ; 34(5): 369-376, 2018 Oct 01.
Artículo en Inglés | MEDLINE | ID: mdl-29651902

RESUMEN

Overuse injuries in the shoulders and lower back are hypothesized to be common in cross-country sit-skiing. Athletes with reduced trunk muscle control mainly sit with the knees higher than the hips (KH). To reduce spinal flexion, a position with the knees below the hips (KL) was enabled for these athletes using a frontal trunk support. The aim of the study was to compare the shoulder joint (glenohumeral joint) and L4-L5 joint reactions of the KL and KH sitting positions. Five able-bodied female athletes performed submaximal and maximal exercise tests in the sitting positions KL and KH on a ski ergometer. Measured pole forces and 3-dimensional kinematics served as input for inverse-dynamics simulations to compute the muscle forces and joint reactions in the shoulder and L4-L5 joint. This was the first musculoskeletal simulation study of seated double poling. The results showed that the KH position was favorable for higher performance and decreased values of the shoulder joint reactions for female able-bodied athletes with full trunk control. The KL position was favorable for lower L4-L5 joint reactions and might therefore reduce the risk of lower back injuries. These results indicate that it is hard to optimize both performance and safety in the same sit-ski.


Asunto(s)
Rendimiento Atlético/fisiología , Postura/fisiología , Rango del Movimiento Articular/fisiología , Articulación del Hombro/fisiología , Esquí/fisiología , Silla de Ruedas , Adulto , Traumatismos de la Espalda/fisiopatología , Traumatismos de la Espalda/prevención & control , Fenómenos Biomecánicos/fisiología , Ergometría , Prueba de Esfuerzo , Femenino , Voluntarios Sanos , Humanos , Lesiones del Hombro/fisiopatología , Lesiones del Hombro/prevención & control , Esquí/lesiones , Equipo Deportivo
8.
Int J Cancer ; 142(11): 2254-2262, 2018 06 01.
Artículo en Inglés | MEDLINE | ID: mdl-29322512

RESUMEN

Inflammation is a well-documented driver of cancer development and progression. However, little is known about its role in prostate carcinogenesis. Thus, we examined the association of C-reactive protein (CRP), haptoglobin, albumin and white blood cells (WBC) with prostate cancer (PCa) severity (defined by PCa risk category and clinicopathological characteristics) and progression (defined by PCa death). We selected 8,471 Swedish men with newly diagnosed PCa who had exposure measurements taken approximately 14 years prior to diagnosis. We calculated odds ratio (OR) and 95% confidence interval (CI) for the associations between the inflammatory markers and PCa severity using logistic regression, while Cox proportional hazard regression was used for the associations with overall and PCa death. Serum CRP levels were associated with increased odds of high risk and metastatic PCa, and high PSA levels (≥20 µg/L) (OR: 1.29; 95% CI: 1.06-1.56, 1.32; 1.05-1.65 and 1.51; 1.26-1.81, respectively). Similarly, higher haptoglobin levels were associated with increased odds of metastatic PCa, high PSA level and possibly high grade PCa (1.38; 1.10-1.74, 1.50; 1.17-1.93 and 1.25; 1.00-1.56, respectively). Albumin was positively associated with Gleason 4 + 3 tumour (1.38; 1.02-1.86) and overall death (HRunit increase in log : 1.60; 95% CI: 1.11-2.30), but inversely associated with high risk PCa and high PSA levels (≥20 µg/L) (0.71; 0.56-0.89 and 0.72; 0.5 9-0.90). WBC was associated with increased odds of T3-T4 PCa. Except for albumin, none of these markers were associated with PCa death or overall death. Systemic inflammation as early as 14 years prior to diagnosis may influence prostate cancer severity.


Asunto(s)
Biomarcadores/sangre , Mediadores de Inflamación/sangre , Neoplasias de la Próstata/sangre , Neoplasias de la Próstata/epidemiología , Anciano , Proteína C-Reactiva , Haptoglobinas , Humanos , Recuento de Leucocitos , Masculino , Persona de Mediana Edad , Mortalidad , Clasificación del Tumor , Oportunidad Relativa , Vigilancia de la Población , Pronóstico , Modelos de Riesgos Proporcionales , Neoplasias de la Próstata/diagnóstico , Neoplasias de la Próstata/mortalidad , Sistema de Registros , Índice de Severidad de la Enfermedad , Suecia/epidemiología
9.
Ann Oncol ; 29(2): 377-385, 2018 02 01.
Artículo en Inglés | MEDLINE | ID: mdl-29161337

RESUMEN

Background: Old age at prostate cancer diagnosis has been associated with poor prognosis in several studies. We aimed to investigate the association between age at diagnosis and prognosis, and if it is independent of tumor characteristics, primary treatment, year of diagnosis, mode of detection and comorbidity. Patients and methods: We conducted a nation-wide cohort study including 121 392 Swedish men aged 55-95 years in Prostate Cancer data Base Sweden 3.0 diagnosed with prostate cancer in 1998-2012 and followed for prostate cancer death through 2014. Data were available on age, stage, grade, prostate-specific antigen (PSA)-level, mode of detection, comorbidity, educational level and primary treatment. We used Cox regression to calculate hazard ratios (HRs) and 95% confidence intervals (CIs). Results: With increasing age at diagnosis, men had more comorbidity, fewer PSA-detected cancers, more advanced cancers and were less often treated with curative intent. Among men with high-risk or regionally metastatic disease, the proportion of men with unknown M stage was higher among old men versus young men. During a follow-up of 751 000 person-years, 23 649 men died of prostate cancer. In multivariable Cox-regression analyses stratified by treatment, old age at diagnosis was associated with poorer prognosis among men treated with deferred treatment (HRage 85+ versus 60-64: 7.19; 95% CI: 5.61-9.20), androgen deprivation therapy (HRage 85+ versus 60-64: 1.72; 95% CI: 1.61-1.84) or radical prostatectomy (HRage 75+ versus 60-64: 2.20; 95% CI: 1.01-4.77), but not radiotherapy (HRage 75+ versus 60-64: 1.08; 95% CI: 0.76-1.53). Conclusion: Our findings argue against a strong inherent effect of age on risk of prostate cancer death, but indicate that in current clinical practice, old men with prostate cancer receive insufficient diagnostic workup and subsequent curative treatment.


Asunto(s)
Neoplasias de la Próstata/diagnóstico , Neoplasias de la Próstata/epidemiología , Neoplasias de la Próstata/terapia , Factores de Edad , Anciano , Anciano de 80 o más Años , Antagonistas de Andrógenos/uso terapéutico , Antineoplásicos/uso terapéutico , Estudios de Cohortes , Humanos , Masculino , Persona de Mediana Edad , Modelos de Riesgos Proporcionales , Prostatectomía/mortalidad , Radioterapia/mortalidad , Suecia/epidemiología
10.
Leukemia ; 32(4): 986-995, 2018 04.
Artículo en Inglés | MEDLINE | ID: mdl-29263438

RESUMEN

Duration of initial disease response remains a strong prognostic factor in multiple myeloma (MM) particularly for upfront autologous hematopoietic cell transplant (AHCT) recipients. We hypothesized that new drug classes and combinations employed prior to AHCT as well as after post-AHCT relapse may have changed the natural history of MM in this population. We analyzed the Center for International Blood and Marrow Transplant Research database to track overall survival (OS) of MM patients receiving single AHCT within 12 months after diagnosis (N=3256) and relapsing early post-AHCT (<24 months), and to identify factors predicting for early vs late relapses (24-48 months post-AHCT). Over three periods (2001-2004, 2005-2008, 2009-2013), patient characteristics were balanced except for lower proportion of Stage III, higher likelihood of one induction therapy with novel triplets and higher rates of planned post-AHCT maintenance over time. The proportion of patients relapsing early was stable over time at 35-38%. Factors reducing risk of early relapse included lower stage, chemosensitivity, transplant after 2008 and post-AHCT maintenance. Shorter post-relapse OS was associated with early relapse, IgA MM, Karnofsky <90, stage III, >1 line of induction and lack of maintenance. Post-AHCT early relapse remains a poor prognostic factor, even though outcomes have improved over time.


Asunto(s)
Mieloma Múltiple/patología , Adulto , Anciano , Anciano de 80 o más Años , Femenino , Trasplante de Células Madre Hematopoyéticas/métodos , Humanos , Inmunoglobulina A/metabolismo , Masculino , Persona de Mediana Edad , Mieloma Múltiple/metabolismo , Recurrencia Local de Neoplasia/metabolismo , Recurrencia Local de Neoplasia/patología , Pronóstico , Recurrencia , Trasplante Autólogo/métodos , Adulto Joven
11.
Bone Marrow Transplant ; 52(12): 1616-1622, 2017 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-28920949

RESUMEN

Autologous hematopoietic cell transplantation (AHCT) in multiple myeloma (MM) patients with renal insufficiency (RI) is controversial. Patients who underwent AHCT for MM between 2008 and 2013 were identified (N=1492) and grouped as normal/mild (⩾60 mL/min), N=1240, moderate (30-59), N=185 and severe RI (<30), N=67 based on Modification of Diet in Renal Disease. Multivariate analyses of non-relapse mortality (NRM), relapse, PFS and overall survival (OS) were performed. Of the 67 patients with severe RI, 35 were on dialysis prior to AHCT. Patients received melphalan 200 mg/m2 (Mel 200) in 92% (normal/mild), 75% (moderate) and 33% (severe) RI; remainder received 140 mg/m2 (Mel 140). Thirty four of 35 patients with severe RI achieved post-AHCT dialysis independence. The 5-year PFS for normal, moderate and severe RI was 35 (95% CI, 31-38)%, 40 (31-49)% and 27 (15-40)%, respectively, (P=0.42); 5-year OS for normal, moderate and severe RI was 68 (65-71)%, 68 (60-76)% and 60 (46-74)%, respectively, (P=0.69). With moderate RI, 5-year PFS for high-dose melphalan 140 mg/m2 was 18 (6-35)% and for Mel 200 was 46 (36-57)% (P=0.009). With severe RI, 5-year PFS Mel 140 was 25 (11-41) % and for Mel 200 was 32 (11-58)% (P=0.37). We conclude that AHCT is safe and effective in patients with MM with RI.


Asunto(s)
Trasplante de Células Madre Hematopoyéticas/métodos , Mieloma Múltiple/terapia , Insuficiencia Renal/complicaciones , Adulto , Anciano , Femenino , Humanos , Masculino , Melfalán/administración & dosificación , Melfalán/uso terapéutico , Persona de Mediana Edad , Mieloma Múltiple/complicaciones , Mieloma Múltiple/mortalidad , Agonistas Mieloablativos/administración & dosificación , Análisis de Supervivencia , Trasplante Autólogo , Adulto Joven
12.
Stat Med ; 36(13): 2100-2119, 2017 06 15.
Artículo en Inglés | MEDLINE | ID: mdl-28233395

RESUMEN

Survival data analysis becomes complex when the proportional hazards assumption is violated at population level or when crude hazard rates are no longer estimators of marginal ones. We develop a Bayesian survival analysis method to deal with these situations, on the basis of assuming that the complexities are induced by latent cohort or disease heterogeneity that is not captured by covariates and that proportional hazards hold at the level of individuals. This leads to a description from which risk-specific marginal hazard rates and survival functions are fully accessible, 'decontaminated' of the effects of informative censoring, and which includes Cox, random effects and latent class models as special cases. Simulated data confirm that our approach can map a cohort's substructure and remove heterogeneity-induced informative censoring effects. Application to data from the Uppsala Longitudinal Study of Adult Men cohort leads to plausible alternative explanations for previous counter-intuitive inferences on prostate cancer. The importance of managing cardiovascular disease as a comorbidity in women diagnosed with breast cancer is suggested on application to data from the Swedish Apolipoprotein Mortality Risk Study. Copyright © 2017 John Wiley & Sons, Ltd.


Asunto(s)
Modelos Estadísticos , Medición de Riesgo , Apolipoproteínas/sangre , Teorema de Bayes , Neoplasias de la Mama/complicaciones , Enfermedades Cardiovasculares/sangre , Enfermedades Cardiovasculares/complicaciones , Femenino , Humanos , Estudios Longitudinales , Masculino , Modelos de Riesgos Proporcionales , Neoplasias de la Próstata/epidemiología , Neoplasias de la Próstata/etiología , Medición de Riesgo/métodos , Medición de Riesgo/estadística & datos numéricos , Factores de Riesgo , Análisis de Supervivencia , Suecia/epidemiología
14.
Eur J Cancer ; 67: 57-65, 2016 11.
Artículo en Inglés | MEDLINE | ID: mdl-27614164

RESUMEN

BACKGROUND: Breast-conserving surgery (BCS) followed by radiotherapy (RT) is an established treatment for women with T1-2N0 breast cancers. Since subgroups of patients have low ipsilateral breast tumour recurrence (IBTR) rates, it is important to study whether RT is necessary for all patients. PATIENTS AND METHODS: A total of 1187 women with primary T1-2N0M0 breast cancer were randomised, after standardised sector resection, to postoperative whole breast RT or no local treatment. Adjuvant systemic therapy was offered to patients with stage II cancers. Patients were followed with clinical examinations and annual mammography for 10 years and thereafter referred to the Swedish mammography screening program. RESULTS: After 15 years of follow-up, a higher cumulative incidence of IBTR was observed in control patients, 23.9%, versus irradiated patients, 11.5%, P<0.001. Recurrence-free survival was inferior, 51.7% versus 60.4%, P=0.0013. The main effect of RT was seen during the first 5 years. However, overall survival was not significantly lower 68.4% versus 71.1%, P=0.68, nor was breast cancer-specific mortality significantly higher. CONCLUSIONS: RT after BCS significantly reduced the incidence of IBTR at 15 years of follow-up. We were unable to identify subgroups which could be spared RT. Breast cancer mortality was not significantly reduced after RT. Good predictive markers for radiation sensitivity and improved adjuvant systemic therapy are needed to omit RT after BCS.


Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Neoplasias de la Mama/terapia , Antagonistas de Estrógenos/uso terapéutico , Mastectomía Segmentaria/métodos , Recurrencia Local de Neoplasia/epidemiología , Radioterapia Adyuvante/métodos , Tamoxifeno/uso terapéutico , Adulto , Anciano , Neoplasias de la Mama/mortalidad , Neoplasias de la Mama/patología , Quimioterapia Adyuvante , Ciclofosfamida/administración & dosificación , Supervivencia sin Enfermedad , Femenino , Fluorouracilo/administración & dosificación , Estudios de Seguimiento , Humanos , Estudios Longitudinales , Escisión del Ganglio Linfático , Metotrexato/administración & dosificación , Persona de Mediana Edad , Estadificación de Neoplasias , Suecia/epidemiología , Carga Tumoral
15.
Bone Marrow Transplant ; 51(10): 1330-1336, 2016 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-27214069

RESUMEN

Chemotherapeutic agents without cross-resistance to prior therapies may enhance PBSC collection and improve patient outcomes by exacting a more potent direct antitumor effect before autologous stem cell transplant. Bendamustine has broad clinical activity in transplantable lymphoid malignancies, but concern remains over the potential adverse impact of this combined alkylator-nucleoside analog on stem cell mobilization. We performed a prospective, nonrandomized phase II study including 34 patients with multiple myeloma (MM) (n=34; International Staging System (ISS) stages I (35%), II (29%) and III (24%); not scored (13%)) to evaluate bendamustine's efficacy and safety as a stem cell mobilizing agent. Patients received bendamustine (120 mg/m2 IV days 1, 2), etoposide (200 mg/m2 IV days 1-3) and dexamethasone (40 mg PO days 1- 4) (bendamustine, etoposide and dexamethasone (BED)) followed by filgrastim (10 µg/kg/day SC; through collection). All patients (100%) successfully yielded stem cells (median of 21.60 × 106/kg of body weight; range 9.24-55.5 × 106/kg), and 88% required a single apheresis. Six nonhematologic serious adverse events were observed in 6 patients including: neutropenic fever (1, grade 3), bone pain (1, grade 3) and renal insufficiency (1, grade 1). In conclusion, BED safely and effectively mobilizes hematopoietic stem cells.


Asunto(s)
Clorhidrato de Bendamustina/administración & dosificación , Dexametasona/administración & dosificación , Etopósido/administración & dosificación , Movilización de Célula Madre Hematopoyética/métodos , Mieloma Múltiple/terapia , Trasplante de Células Madre de Sangre Periférica/métodos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Femenino , Movilización de Célula Madre Hematopoyética/efectos adversos , Humanos , Masculino , Persona de Mediana Edad , Trasplante Autólogo , Resultado del Tratamiento
16.
Bone Marrow Transplant ; 51(1): 67-71, 2016 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-26367217

RESUMEN

We aimed to examine whether doses of melphalan higher than 200 mg/m(2) improve response rates when used as conditioning before autologous transplant (ASCT) in multiple myeloma (MM) patients. Patients with MM, n=131, were randomized to 200 mg/m(2) (mel200) vs 280 mg/m(2) (mel280) using amifostine pretreatment. The primary end point was the proportion of patients achieving near complete response (⩾nCR). No treatment-related deaths occurred in this study. Responses following ASCT were for mel200 vs mel280, respectively, ⩾nCR 22 vs 39%, P=0.03, ⩾PR 57 vs 74%, P=0.04. The hazard of mortality was not statistically significantly different between groups (mel200 vs mel280; hazard ratio (HR)=1.15 (95% confidence interval (CI), 0.62-2.13, P=0.66)) nor was the rate of progression/mortality (HR=0.81 (0.52-1.27, P=0.36)). The estimated PFS at 1 and 3 years were 83 and 46%, respectively, for mel200 and 78 and 54%, respectively, for mel280. Amifostine and mel280 were well tolerated, with no grade 4 regimen-related toxicities and only one grade 3 mucositis (none with mel200) and three grade 3 gastrointestinal (GI) toxicities (two in mel200). Hospitalization rates were more frequent in the mel280 group (59 vs 43%, P=0.08). Mel280 resulted in a higher major response rate (CR+nCR) and should be evaluated in larger studies.


Asunto(s)
Melfalán/administración & dosificación , Mieloma Múltiple/mortalidad , Mieloma Múltiple/terapia , Trasplante de Células Madre , Acondicionamiento Pretrasplante , Adulto , Anciano , Autoinjertos , Supervivencia sin Enfermedad , Femenino , Humanos , Masculino , Persona de Mediana Edad , Mieloma Múltiple/patología , Tasa de Supervivencia
18.
Ann Oncol ; 26(11): 2323-8, 2015 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-26347113

RESUMEN

BACKGROUND: High-dose therapy and autologous stem cell transplantation (ASCT) improves outcomes for patients with mantle cell lymphoma (MCL), but relapse ultimately occurs in most patients. Recently presented interim results from a phase III prospective trial suggest maintenance rituximab (MR) after ASCT for MCL improves progression-free survival (PFS). The maturation of these data and any benefit of MR on overall survival (OS) remain to be defined. PATIENTS AND METHODS: In this retrospective study, we examined a cohort of consecutive patients with MCL that underwent ASCT for MCL at our center and evaluated their outcomes according to whether they received MR after ASCT (n = 50) or did not (n = 107). MR was treated as a time-dependent covariate to account for variation in timing of its initiation. RESULTS: MR was associated with an improved PFS [hazard ratio (HR) 0.44; confidence interval (CI) (0.24-0.80), P = 0.007] and overall survival (OS; HR 0.46; CI 0.23-0.93, P = 0.03) following a multivariate adjustment for confounding factors with a median follow-up of ∼5 years. Grade 4 neutropenia was increased (34% versus 18%, P = 0.04) in the MR group, but no effect on the rate of mortality unrelated to relapse was observed. CONCLUSIONS: These data support that MR after ASCT for MCL confers a benefit in PFS and additionally suggest it may improve OS. General application of this strategy will require confirmation of benefit in prospective randomized trials.


Asunto(s)
Trasplante de Células Madre Hematopoyéticas/tendencias , Linfoma de Células del Manto/diagnóstico , Linfoma de Células del Manto/terapia , Quimioterapia de Mantención/tendencias , Rituximab/administración & dosificación , Adulto , Anciano , Antineoplásicos/administración & dosificación , Estudios de Cohortes , Terapia Combinada/métodos , Terapia Combinada/tendencias , Supervivencia sin Enfermedad , Femenino , Estudios de Seguimiento , Trasplante de Células Madre Hematopoyéticas/métodos , Humanos , Quimioterapia de Mantención/métodos , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Trasplante Autólogo/métodos , Trasplante Autólogo/tendencias
19.
Ann Oncol ; 26(10): 2125-32, 2015 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-26199392

RESUMEN

BACKGROUND: High-dose chemotherapy (HDC) using sequential cycles of carboplatin/etoposide is curative for relapsed germ-cell tumors (GCT). However, outcomes of high-risk patients in advanced relapse remain poor. We previously developed a new HDC regimen combining infusional gemcitabine with docetaxel/melphalan/carboplatin (GemDMC), with preliminary high activity in refractory GCT. Given the high vascular endothelial growth factor expression in metastatic GCT and the synergy between bevacizumab and chemotherapy, we studied concurrent bevacizumab and sequential HDC using GemDMC and ifosfamide/carboplatin/etoposide (ICE) in patients with poor-risk relapsed or refractory disease. PATIENTS AND METHODS: Eligibility criteria included intermediate/high-risk relapse (Beyer Model), serum creatinine ≤ 1.8 mg/dl and adequate pulmonary/cardiac/hepatic function. Patients received sequential HDC cycles with bevacizumab preceding GemDMC (cycle 1) and ICE (cycle 2). The trial was powered to distinguish a target 50% 2-year relapse-free survival (RFS) from an expected 25% 2-year RFS in this population. RESULTS: We enrolled 43 male patients, median age 30 (20-49) years, with absolute refractory (N = 20), refractory (N = 17) or cisplatin-sensitive (N = 6) disease, after a median 3 (1-5) prior relapses. Disease status right before HDC was unresponsive (N = 24, progressive disease 22, stable disease 2), partial response with positive markers (PRm(+)) (N = 8), PRm(-) (N = 7) or complete response (N = 4). Main toxicities were mucositis and renal. Four patients (three with baseline marginal renal function) died from HDC-related complications. Tumor markers normalized in 85% patients. Resection of residual lesions (N = 13) showed necrosis (N = 4), mature teratoma (N = 2), necrosis/teratoma (N = 3) and viable tumor (N = 4). At median follow-up of 46 (9-84) months, the RFS and overall survival rates are 55.8% and 58.1%, respectively. CONCLUSIONS: Sequential bevacizumab/GemDMC-bevacizumab/ICE shows encouraging outcomes in heavily pretreated and refractory GCT, exceeding the results expected in this difficult to treat population. CLINICALTRIALSGOV: NCT00936936.


Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Resistencia a Antineoplásicos , Trasplante de Células Madre Hematopoyéticas , Neoplasias del Mediastino/terapia , Recurrencia Local de Neoplasia/terapia , Neoplasias de Células Germinales y Embrionarias/terapia , Neoplasias Retroperitoneales/terapia , Neoplasias Testiculares/terapia , Adolescente , Adulto , Anciano , Bevacizumab/administración & dosificación , Carboplatino/administración & dosificación , Niño , Cisplatino/administración & dosificación , Terapia Combinada , Desoxicitidina/administración & dosificación , Desoxicitidina/análogos & derivados , Etopósido/administración & dosificación , Femenino , Estudios de Seguimiento , Humanos , Ifosfamida/administración & dosificación , Masculino , Neoplasias del Mediastino/mortalidad , Neoplasias del Mediastino/patología , Persona de Mediana Edad , Invasividad Neoplásica , Metástasis de la Neoplasia , Recurrencia Local de Neoplasia/mortalidad , Recurrencia Local de Neoplasia/patología , Estadificación de Neoplasias , Neoplasias de Células Germinales y Embrionarias/mortalidad , Neoplasias de Células Germinales y Embrionarias/patología , Pronóstico , Neoplasias Retroperitoneales/mortalidad , Neoplasias Retroperitoneales/patología , Terapia Recuperativa , Tasa de Supervivencia , Neoplasias Testiculares/mortalidad , Neoplasias Testiculares/patología , Trasplante Autólogo , Adulto Joven , Gemcitabina
20.
Bone Marrow Transplant ; 50(5): 663-7, 2015 May.
Artículo en Inglés | MEDLINE | ID: mdl-25730190

RESUMEN

Outcomes in multiple myeloma (MM) have improved significantly with novel agent therapy and autologous stem cell transplantation (ASCT). ASCTs are typically planned as either tandem or a single transplant with additional stored PBSCs available for a second salvage transplant. To accommodate these strategies, many centers routinely collect and store adequate PBSCs for two ASCTs. We analyzed the cost associated with this practice by determining the expenses of PBSC collection, cryopreservation and storage, and the ultimate use of additional cryopreserved PBSCs in patients who had undergone at least one ASCT. There were 889 MM patients transplanted between 1993 and 2011 at our center. Most (N=726) had residual PBSCs in storage after their first ASCT (ASCT1). Only 135 patients underwent a second ASCT within a median of 14 months after ASCT1. The percentage of patients receiving a second ASCT declined over time. The resources required to collect and store unused PBSCs added up to 336 extra patient days of apheresis and 41 587 extra patient months of cryopreservation, translating into an average extra cost per patient of US$4981.12. A reconsideration of conventional PBSC collection and storage practices would save significant cost for the majority of MM patients who never undergo a second ASCT.


Asunto(s)
Eliminación de Componentes Sanguíneos , Criopreservación , Mieloma Múltiple , Trasplante de Células Madre de Sangre Periférica , Adulto , Anciano , Autoinjertos , Eliminación de Componentes Sanguíneos/economía , Eliminación de Componentes Sanguíneos/métodos , Costos y Análisis de Costo , Criopreservación/economía , Criopreservación/métodos , Femenino , Estudios de Seguimiento , Humanos , Masculino , Persona de Mediana Edad , Mieloma Múltiple/economía , Mieloma Múltiple/terapia , Trasplante de Células Madre de Sangre Periférica/economía , Trasplante de Células Madre de Sangre Periférica/métodos , Estudios Retrospectivos
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